Dichloromethane → 1-(4-Ethylcyclohexyl)-3-(1-isobutyrylpiperidin-4-yl)urea

HRID 574688Notes

Reaction equation

F[C:2](F)(F)[C:3]1[CH:8]=[CH:7][C:6]([N:9]=[C:10]=[O:11])=[CH:5][CH:4]=1.[NH2:14][CH:15]1[CH2:20][CH2:19][N:18]([C:21](=[O:26])[CH:22]([CH3:25])[CH2:23]C)[CH2:17][CH2:16]1.[CH2:27](Cl)Cl>>[CH2:2]([CH:3]1[CH2:8][CH2:7][CH:6]([NH:9][C:10]([NH:14][CH:15]2[CH2:20][CH2:19][N:18]([C:21](=[O:26])[CH:22]([CH3:25])[CH3:23])[CH2:17][CH2:16]2)=[O:11])[CH2:5][CH2:4]1)[CH3:27]

Participants

Reactant 3

HCID 6344Dichloromethane

HCID 737684-(Trifluoromethyl)phenyl isocyanate

HCID 167829341-(4-Amino-1-piperidinyl)-2-methyl-1-butanone

Product 1

HCID 716780091-(4-Ethylcyclohexyl)-3-(1-isobutyrylpiperidin-4-yl)ureaYield 42%

Procedure

4-(Trifluoromethyl)phenylisocyanate (100 mg, 0.65 mmol) and 1-(4-aminopiperidin-1-yl)-2-methylbutan-1-one (111 mg, 0.53 mmol) was dissolved in CH2Cl2 (100 mL) and stirred for 12 h. The reaction was quenched by addition of water. The organic layer was isolated and the aqueous layer was extracted with EtOAc for 4 times. The combined organic layer was concentrated under vacuo and was further purified by flash chromatography (EtOAc:Hex/1:1) yielding final product (89 mg, 2.76 mmol, 42%). H-NMR (DMSO-d6) ∂ 0.83 (t, J=8 Hz, 3H), 0.91 (m, 1H), 0.97 (m, 7H), 1.03 (m, 3H), 1.16 (m, 4H), 1.69 (m, 3H), 1.78 (m, 3H), 2.72 (t, J=12 Hz, 1H), 2.85 (m, 1H), 3.10 (t, J=12 Hz, 1H), 3.24 (m, 1H), 3.57 (m, 1H), 3.79 (d, J=13 Hz, 1H), 4.14 (d, J=13 Hz, 1H), 5.56 (d, J=7.5 Hz, 1H), 5.70 (d, J=7.5 Hz, 1H).

Workup

customThe reaction was quenched by addition of water
customThe organic layer was isolated
extractionthe aqueous layer was extracted with EtOAc for 4 times
concentrationThe combined organic layer was concentrated under vacuo
customwas further purified by flash chromatography (EtOAc:Hex/1:1)

Sources & evidence

ORD record: ord-b897d4b10249411582059d8ed0368668
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09034903B2

Reaction notes

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